A. Bertelè

Quantitative electron microscopy of endocrine cells in oxyntic mucosa of normal human stomach

SummaryAn ultrastructural morphometric study of the endocrine cells of the oxyntic mucosa of the stomach in gastric biopsies collected from five male and five female healthy volunteers aged 19–31 was performed. No sex-related differences were disclosed. Endocrine cells accounted for 1.2±0.4% of the epithelial volume and 0.9±0.4% of the mucosal volume, i.e., including the lamina propria. After classification of the specific endocrine cell types according to the ultrastructural morphology of secretory granules, the volume densities of ECL, P and D cells (30±9%, 24±7%, and 22±4% of the entire endocrine cell mass, respectively) were higher than those of other endocrine cell types. In particular, EC cells contributed less than 10% and X cells represented a very low proportion of the total cells. Non-granulated profiles of cells which in all other respects appeared to be endocrine were also found with a volume density of 8±4%. D cells were distinguished by the high fraction of cytoplasm occupied by secretory granules (31±5%). Subdivision of the whole mucosa into four horizontal segments revealed the endocrine cells to be mostly distributed in the three lower, with virtually no endocrine cells in the superficial segment. The quantitative ultrastructural analysis of the endocrine cell population of the normal human oxyntic mucosa provided by this study may allow a better evaluation of physiological and pharmacological variations of the endocrine cell population.

Argyrophil Cell Hyperplasia of Fundic Mucosa in Patients with Chronic Atrophic Gastritis

Eighteen cases of severe hyperplasia of fundic argyrophil cells observed during routine histologic examination of endoscopic gastric biopsy specimens from unselected patients with upper gastro-intestinal symptomatology were investigated. All patients, except one, were female with a mean age of 57 years. Atrophic gastritis of fundic mucosa with severe hypo- or achlorhydria was present in all cases. Hypergastrinaemia (of antral origin) was found in 15 subjects in which circulating gastrin levels were determined. Pernicious anaemia was seen in 1 patient. At light microscopy, the hyperplastic fundic cells were stained by the Grimelius and the Sevier-Munger silver methods and, in approximately 30% of cases, by lead-haematoxylin. In addition, these cells reacted with anti chromogranin antibodies. In 8 of 9 patients studied by electron-microscopy, enterochromaffin-like (ECL) cells were found to be the more frequent cell type. D1 cells prevailed in 1 case and were rare in the others. The frequency of P cells was intermediate between that of ECL cells and that of D1 cells. In conclusion, our observations indicate that: argyrophil cell hyperplasia of atrophic fundic mucosa is prevalently found in women with hypergastrinaemia, and the hyperplastic process involves mostly the ECL type of gastric endocrine cells. It is noteworthy that similar associations have been shown to be present in patients affected by fundic carcinoid tumours and atrophic gastritis.

Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia

Clinical and experimental evidence indicates that carcinoid tumours of the stomach fundic mucosa represent another example of hormone-dependent neoplasm, gastrin being the hormone involved in tumour induction. In this context hyperplasia of fundic endocrine cells associated with chronic atrophic gastritis (CAG) and hypergastrinaemia is regarded as the most frequent preneoplastic lesion. However, the cell type involved in this hyperplasia has not been clarified. To elucidate this problem fundic endocrine cells were characterized ultrastructurally in 9 patients from which endoscopic gastric biopsies were obtained. ECL cells were the most frequent cell type in 8 cases, in 4 of which they were more numerous than all other cell types taken together. D1 cells were the most frequent type in one case while they were inconspicuous in the other cases. P cells were found with a frequency in each case intermediate between that of ECL cells and that of D1 cells. These results indicate that fundic endocrine cell hyperplasia occurring in hypergastrinaemic CAG is in most cases cytologically similar to that found in other hypergastrinemic conditions, in which the gastrin-dependent ECL cells were already found to prevail. They also explain why fundic carcinoids arising in CAG are mostly composed of ECL cells. The relation between ECL, D1 and P cells, if any, remains obscure.

Expression of glycoprotein hormone alpha-subunit by endocrine cells of the oxyntic mucosa is associated with hypergastrinemia

Previous studies have shown that hyperplastic endocrine cells of the oxyntic mucosa in patients with atrophic gastritis may express immunoreactivity for the alpha-subunit of human chorionic gonadotropin (alpha-HCG, common to all glycoprotein hormones). Since this endocrine proliferation is regarded as dependent on the trophic effect of the concomitant hypergastrinemia, the relation between immunohistochemical expression of alpha-HCG by oxyntic endocrine cells and serum levels of gastrin were investigated. The study was performed on endoscopic gastric biopsies of the oxyntic mucosa from 49 patients subdivided into the following groups: A) with histologically normal mucosa and normogastrinemia (22 cases), B) with atrophic gastritis and normogastrinemia (12 cases), C) with normal mucosa and hypergastrinemia (Zollinger-Ellison syndrome, retained antrum) (7 cases) and D) with atrophic gastritis and hypergastrinemia (with or without pernicious anemia) (8 cases). The alpha-HCG immunoreactive cells were found in all hypergastrinemic patients (groups C and D), regardless of the concomitant pathological condition of the mucosa. These cells accounted for 7.8% to 44.7% of the number of Grimelius argyrophil cells in consecutive serial sections. In contrast, alpha-HCG-containing cells were exceptional or absent in most normogastrinemic patients. Their number was sizable in only two cases of group A and three cases of group B, where it ranged from 2.5% to 14.8% of the number of argyrophil cells. It was concluded that expression of alpha-HCG is another feature of oxyntic endocrine cells associated with hypergastrinemia in addition to those previously recognized such as development of hyperplasia and/or carcinoid tumors.

Endocrine cell replacement of oxyntic glands in Zollinger-Ellison syndrome: A role for female sex hormones?

A 48-year-old woman with Zollinger-Ellison syndrome (ZES), but no evidence of multiple endocrine neoplasia (MEN)-1 syndrome, developed an unusually florid evolution of enterochromaffin-like (ECL) cell hyperplasia, which led to extensive replacement of oxyntic glands by endocrine tissue and resulted in the disappearance of the patient’s gastric acid hypersecretion with antisecretory treatment no longer required. The patient’s previous history included breast cancer, treated with surgery and 5 years of antiestrogen therapy, and bilateral granulosa-thecal cell tumor of the ovary. In addition, increased circulating levels of 17 β-estradiol (17βE) and progesterone, possibly depending on concomitant development of liver cirrhosis, were also found. On the basis of these associations, it is suggested that abnormalities in the domain of female sex hormones, with a potential synergistic role of liver dysfunction, may be involved in the florid evolution of hypergastrinemia-driven proliferation of ECL cells observed in the present case.

Probiotics for the Treatment of Symptomatic Uncomplicated Diverticular Disease: Rationale and Current Evidence.

Changes in the colonic microbiota are critical to the pathogenesis of diverticular complications such as diverticulitis and peridiverticular abscesses. However, more subtle changes in microbiota composition may well be important to the more chronic manifestations of diverticulosis. Some studies have shown the presence of bacterial overgrowth in subgroups of patients with diverticular disease and recent studies, using molecular biology techniques, found an increase of proteobacteria and actinobacteria in patients with symptomatic uncomplicated diverticular disease (SUDD), compared with healthy controls. The use of probiotics to modulate intestinal microecology in SUDD appears therefore rational. Although several investigations evaluating the clinical efficacy of probiotics have been performed, no definitive results have yet been achieved, mainly due to the heterogeneity of the available studies. Most of the studies used probiotics in combination with poorly absorbed antimicrobials or anti-inflammatory drugs. In only 4 studies, there was a harm using probiotics alone, but only 1 was a placebo-controlled, double-blind trial. The analysis of the available evidence reveals a poor quality of the published studies, whose design was heterogeneous, with only 2 out of 11 trials being double-blind and randomized. Therefore, available data can only suggest a benefit of probiotics in SUDD, but do not allow any evidence-based definite conclusion. As a consequence, current guidelines state that there is insufficient evidence to recommend probiotics for symptom relief in patients with diverticular disease.

Altérations morphologiques et fonctionnelles muqueuses chez les patients porteurs de polypes gastriques

RésuméL’étude est consacrée à la relation entre polypes gastriques et lésions de la muqueuse (gastrite chronique atrophique, ulcère, cancer).Les résultats, basés sur une revue de 115 polypes épithéliaux, montrent la localisation prédominante des polypes au niveau antral et leur association avec la gastrite chronique atrophique. Cette association, de même que l’existence de foyers de carcinomes intramuqueux, s’observe plus fréquemment dans les polypes adénomateux que dans les lésions hyperplasiques. Des altérations sévères de la muqueuse gastrique ont été démontrées par une réduction importante de la sécrétion acide, spécialement chez les patients porturs de polypes adénomateux.En conclusion, chez de tels patients, ces anomalies de la muqueuse sont aussi importantes que la présence même des polypes.SummaryThe relationship between gastric polyps and gastric mucosal lesions (chronic atrophic gastritis, ulcer, carcinoma) has been studied.The results, based on a review of 115 epithelial polyps, demonstrated that most polyps are localized in the antrum and showed associated chronic atrophic gastritis. This association, as well as foci of intramucosal carcinoma, is found more frequently in patients with adenomatous than in those with hyperplastic polyps.Moreover the pronounced alterations of gastric mucosa have been demonstrated by reduction of gastric acid secretion, especially in patients, with adenomatous polyps.In conclusion, in these patients the gastric mucosal alterations are as important as the presence of polyp.